The proposed project is designed to ascertain specific questions related to the modulation of substrate utilization and growth of the fetus and neonate by the hormone insulin. The majority of the proposal will utilize the chronically catherized fetal sheep as a model of fetal metabolism and growth. The human fetus and infant of the pregnant diabetic may represent a model for the effects of substrate surfeit and endogenous hyperinsulinism upon fetal metabolism. To test the hypothesis that it is the fetal hyperglycemia that induces altered insulin storage and macrosomia, chronic fetal glucose infusions will be performed in one of twin fetal lambs and the effects of infusion upon growth noted. Chronic epxerimental fetal hyperglycemia causes a significant fetal hypoxemia which may be important in gaining an understanding of the mechanisms behind the increased risks of late fetal demise, neurologic impairment and polycythemia seen in some fetuses of diabetic women. Oxygen consumption by uterus-placenta and fetus, hypothesized to rise during hyperglycemic states, will be monitored during glucose infusions in singleton fetal lambs. Effects of glucose vs. fetal hyperinsulinism upon oxygen consumption may be able to be separated using short term fetal infusions of somatostatin to suppress insulin release during fetal hyperglycemia. Insulin may also play a role in altering fetal uptake of amino acids and, therefore, protein synthesis. Using controlled fetal lamb insulin infusions we wish to show that marked fetal hyperinsulinism causes an increase in fetal uptake of amino acids destined for use as fuel and/or protein accretion. Lastly, the role of insulin in modulation of substrates in the neonate, particularly the low birth weight premature infant, is unknown. Because of the limitations of blood sampling in these tiny newborns, we wish to devlop an indirect estimate of insulin release to assess further insulin's role in promoting growth and also as a bioassay to assess adequacy of nutritional intake in these babies. A small but measurable fraction of blood insulin is excreted unchanged in the urine and can be measured easily in both adult and neonate. By assessing urinary insulin excretion in the premature infant and correcting for varying degrees of renal maturation, we hope to show that increasing caloric intake and weight gain are associated with increasing insulin excretion.